Exelixis,
Inc.
(Nasdaq: EXEL) and Ipsen (Euronext:IPN; ADR:IPSEY) today
announced the initiation of COSMIC-312, a phase 3 pivotal trial of
cabozantinib (CABOMETYX®) in combination with atezolizumab (TECENTRIQ®)
versus sorafenib in previously untreated advanced hepatocellular
carcinoma (HCC). The co-primary endpoints of the trial are
progression-free survival and overall survival. An exploratory arm will
also evaluate cabozantinib monotherapy in this first-line setting.

“Liver cancer is the fastest-rising cause of cancer-related death in the
U.S., underscoring the need for new treatment options for this patient
community,” said Gisela Schwab, M.D., President, Product Development and
Medical Affairs and Chief Medical Officer, Exelixis. “Based on past
evidence of potential synergistic effects with cabozantinib and immune
checkpoint inhibitors, the combination offers promise for patients with
advanced liver cancer who have not received prior treatment.”

COSMIC-312 is a multicenter, randomized, controlled phase 3 pivotal
trial that aims to enroll approximately 640 patients at up to 200 sites
globally. Patients will be randomized 6:3:1 to one of three arms:
cabozantinib (40 mg) and atezolizumab, sorafenib, or cabozantinib (60
mg).

Exelixis is sponsoring COSMIC-312, and Ipsen will co-fund the trial.
Ipsen will have access to the results to support potential future
regulatory submissions outside of the U.S. and Japan. Genentech, a
member of the Roche Group, is providing atezolizumab for use in this
trial.

“With more than 800,000 new diagnoses of liver cancer worldwide each
year and a poor prognosis for patients with advanced disease, there is
an urgent need to identify new treatment options,” said R. Kate Kelley,
M.D., Associate Professor of Clinical Medicine, Division of
Hematology/Oncology, University of California, San Francisco, and lead
investigator on COSMIC-312. “We look forward to learning whether the
combination of cabozantinib and atezolizumab may improve outcomes for
previously untreated patients.”

Liver cancer is the second-leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and 800,000 new cases each year.1
In the U.S., the incidence of liver cancer has more than tripled since
1980.2
HCC is the most common form of liver cancer, making up
about three-fourths of the estimated nearly 42,000 new cases in the U.S.
in 2018.2
HCC is the fastest-rising cause of cancer-related
death in U.S.3
According to the GLOBOCAN data, it is
estimated that across the European Union (EU-28) nearly 60,000 new
patients will be diagnosed with liver cancer in 2020.4
Without treatment, patients with advanced HCC usually survive less than
6 months.5

About CABOMETYX® (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced RCC. On May 29, 2018, Exelixis announced that the
U.S. Food and Drug Administration accepted for filing the supplemental
New Drug Application for CABOMETYX for previously treated advanced HCC
and assigned a Prescription Drug User Fee Act action date of January 14,
2019. In March 2017, the FDA granted orphan drug designation to
cabozantinib for the treatment of advanced HCC.

CABOMETYX tablets are also approved in: the European Union, Norway,
Iceland, Australia, Switzerland, South Korea, Canada, Brazil and Taiwan
for the treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy; in the European Union for previously untreated
intermediate- or poor-risk advanced RCC; in Canada for adult patients
with advanced RCC who have received prior VEGF targeted therapy; and in
the European Union, Norway and Iceland for HCC in adults who have
previously been treated with sorafenib.

CABOMETYX is not indicated for previously untreated advanced HCC.

About Exelixis’ Collaboration with Ipsen

On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications outside of the United States, Canada and Japan.
On December 21, 2016, this agreement was amended to include
commercialization rights for Ipsen in Canada. Ipsen has opted to
participate in this phase 3 trial in first-line advanced HCC and will
have access to the results to support potential future regulatory
submissions. They may also participate in future studies at their
choosing.

About Exelixis’ Collaboration with Takeda

On January 30, 2017, Exelixis and Takeda jointly announced an exclusive
licensing agreement for the commercialization and further development of
cabozantinib indications in Japan. Under the parties’ collaboration
agreement, if Takeda opts to participate in funding this phase 3 trial,
or future studies, Takeda will have access to the respective study
results to support potential future regulatory submissions in their
territory.

Exelixis holds the exclusive rights to develop and commercialize
cabozantinib in the United States.

Please see important safety information below. For more information,
see the regularly updated registered product information on the European
Medicine Agency www.ema.europa.eu

Indications
: CABOMETYX® is indicated for the treatment of
advanced renal cell carcinoma (RCC) in treatment-naïve adults with
intermediate or poor risk or in adults following prior vascular
endothelial growth factor (VEGF)-targeted therapy

Dosage and Administration
: The recommended dose of CABOMETYX® is
60 mg once daily. Treatment should continue until the patient is no
longer clinically benefiting from therapy or until unacceptable toxicity
occurs. Management of suspected adverse drug reactions may require
temporary interruption and/or dose reduction of CABOMETYX® therapy. For
dose modification, please refer to full SmPC. CABOMETYX® is for oral
use. The tablets should be swallowed whole and not crushed. Patients
should be instructed to not eat anything for at least 2 hours before
through 1 hour after taking CABOMETYX®.

Contraindications
: Hypersensitivity to the active substance or to
any of the excipients listed in the SmPC.

Special warnings and precautions for use:

Monitor closely for toxicity during first 8 weeks of therapy. Events
that generally have early onset include hypocalcaemia, hypokalaemia,
thrombocytopenia, hypertension, palmar-plantar erythrodysaesthesia
syndrome (PPES), proteinuria, and gastrointestinal (GI) events.
Perforations and fistulas: serious gastrointestinal perforations and
fistulas, sometimes fatal, have been observed with cabozantinib.
Patients with inflammatory bowel disease, GI tumour infiltration or
complications from prior GI surgery should be evaluated prior to therapy
and monitored; if perforation and unmanageable fistula occur,
discontinue cabozantinib.

Thromboembolic events
: use with caution in patients with a
history of or risk factors for thromboembolism; discontinue if acute
myocardial infarction (MI) or other significant arterial thromboembolic
complication occurs.

Haemorrhage
: not recommended for patients that have or are at
risk of severe haemorrhage. Wound complications: treatment should be
stopped at least 28 days prior to scheduled surgery (including dental).

Women of childbearing potential/contraception in males and females
:
Ensure effective measures of contraception (oral contraceptive plus a
barrier method) in male and female patients and their partners during
therapy and for at least 4 months after treatment.

Pregnancy and lactation
: CABOMETYX should not be used during
pregnancy unless the clinical condition of the woman requires treatment.
Lactation – discontinue breast-feeding during and for at least 4 months
after completing treatment. Drive and use machines: Caution is
recommended.

For more information, see the regularly updated registered product
information on the European Medicine Agency www.ema.europa.eu

About Exelixis

Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially
successful, oncology-focused biotechnology company that strives to
accelerate the discovery, development and commercialization of new
medicines for difficult-to-treat cancers. Following early work in model
genetic systems, we established a broad drug discovery and development
platform that has served as the foundation for our continued efforts to
bring new cancer therapies to patients in need. We discovered our three
commercially available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib) and COTELLIC® (cobimetinib), and have entered into
partnerships with leading pharmaceutical companies to bring these
important medicines to patients worldwide. Supported by revenues from
our marketed products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our pipeline.
We are supplementing our existing therapeutic assets with targeted
business development activities and internal drug discovery – all to
deliver the next generation of Exelixis medicines and help patients
recover stronger and live longer. Exelixis is a member of Standard &
Poor’s (S&P) MidCap 400 index, which measures the performance of
profitable mid-sized companies. For more information about Exelixis,
please visit www.exelixis.com
,
follow @ExelixisInc
on Twitter or like Exelixis,
Inc.
on Facebook.

About Ipsen

Ipsen is a global biopharmaceutical group focused on innovation and
specialty care. The group develops and commercializes innovative
medicines in three key therapeutic areas - Oncology, Neuroscience and
Rare Diseases. Its commitment to Oncology is exemplified through its
growing portfolio of key therapies for prostate cancer, neuroendocrine
tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a
well-established Consumer Healthcare business. With total sales over
€1.9 billion in 2017, Ipsen sells more than 20 drugs in over 115
countries, with a direct commercial presence in more than 30 countries.
Ipsen's R&D is focused on its innovative and differentiated
technological platforms located in the heart of the leading
biotechnological and life sciences hubs (Paris-Saclay, France; Oxford,
UK; Cambridge, US). The Group has about 5,400 employees worldwide. Ipsen
is listed in Paris (Euronext: IPN) and in the United States through a
Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For
more information on Ipsen, visit www.ipsen.com
.

Exelixis Forward-Looking Statements

This press release contains forward-looking statements, including,
without limitation, statements related to: the potential of the
combination of cabozantinib and atezolizumab, or of cabozantinib as a
monotherapy, as treatment options for patients with previously untreated
advanced HCC; and Exelixis’ plans to reinvest in its business to
maximize the potential of the company’s pipeline, including through
targeted business development activities and internal drug discovery.
Any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements and are based upon Exelixis’ current plans, assumptions,
beliefs, expectations, estimates and projections. Forward-looking
statements involve risks and uncertainties. Actual results and the
timing of events could differ materially from those anticipated in the
forward-looking statements as a result of these risks and uncertainties,
which include, without limitation: risks and uncertainties related to
regulatory review and approval processes and Exelixis’ compliance with
applicable legal and regulatory requirements; the potential failure of
the combination of cabozantinib and atezolizumab, or of cabozantinib as
a monotherapy, to demonstrate safety and/or efficacy in COSMIC-312;
uncertainties inherent in the product development process, including
evolving regulatory requirements, slower than anticipated patient
enrollment or inability to identify a sufficient number of clinical
trial sites; the costs of conducting clinical trials, including the
ability or willingness of Exelixis’ collaboration partners to invest in
the resources necessary to complete the trials; Exelixis’ dependence on
third-party vendors for the development, manufacture and supply of
cabozantinib; Exelixis’ ability to protect its intellectual property
rights; market competition; changes in economic and business conditions;
and other factors affecting Exelixis and its development programs
discussed under the caption “Risk Factors” in Exelixis’ Quarterly Report
on Form 10-Q filed with the Securities and Exchange Commission (SEC) on
November 1, 2018, and in Exelixis’ future filings with the SEC. All
forward-looking statements in this press release are based on
information available to Exelixis as of the date of this press release,
and Exelixis undertakes no obligation to update or revise any
forward-looking statements contained herein.

Ipsen Forward-Looking Statement

The forward-looking statements, objectives and targets contained herein
are based on the Group’s management strategy, current views and
assumptions. Such statements involve known and unknown risks and
uncertainties that may cause actual results, performance or events to
differ materially from those anticipated herein. All of the above risks
could affect the Group’s future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic conditions
based on the information available today. Use of the words "believes",
"anticipates" and "expects" and similar expressions are intended to
identify forward-looking statements, including the Group’s expectations
regarding future events, including regulatory filings and
determinations. Moreover, the targets described in this document were
prepared without taking into account external growth assumptions and
potential future acquisitions, which may alter these parameters. These
objectives are based on data and assumptions regarded as reasonable by
the Group. These targets depend on conditions or facts likely to happen
in the future, and not exclusively on historical data. Actual results
may depart significantly from these targets given the occurrence of
certain risks and uncertainties, notably the fact that a promising
product in early development phase or clinical trial may end up never
being launched on the market or reaching its commercial targets, notably
for regulatory or competition reasons. The Group must face or might face
competition from generic products that might translate into a loss of
market share. Furthermore, the Research and Development process involves
several stages each of which involves the substantial risk that the
Group may fail to achieve its objectives and be forced to abandon its
efforts with regards to a product in which it has invested significant
sums. Therefore, the Group cannot be certain that favorable results
obtained during pre-clinical trials will be confirmed subsequently
during clinical trials, or that the results of clinical trials will be
sufficient to demonstrate the safe and effective nature of the product
concerned. There can be no guarantees a product will receive the
necessary regulatory approvals or that the product will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements. Other risks and
uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation; global
trends toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent in new
product development, including obtaining regulatory approval; the
Group's ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of the Group’s patents and other protections for
innovative products; and the exposure to litigation, including patent
litigation, and/or regulatory actions. The Group also depends on third
parties to develop and market some of its products which could
potentially generate substantial royalties; these partners could behave
in such ways which could cause damage to the Group’s activities and
financial results. The Group cannot be certain that its partners will
fulfil their obligations. It might be unable to obtain any benefit from
those agreements. A default by any of the Group’s partners could
generate lower revenues than expected. Such situations could have a
negative impact on the Group’s business, financial position or
performance. The Group expressly disclaims any obligation or undertaking
to update or revise any forward-looking statements, targets or estimates
contained in this press release to reflect any change in events,
conditions, assumptions or circumstances on which any such statements
are based, unless so required by applicable law. The Group’s business is
subject to the risk factors outlined in its registration documents filed
with the French Autorité des Marchés Financiers. The risks and
uncertainties set out are not exhaustive and the reader is advised to
refer to the Group’s 2017 Registration Document available on its website
(www.ipsen.com
).

Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.

TECENTRIQ® (atezolizumab) is a registered trademark of Genentech, a
member of the Roche Group.

The information stated above was prepared by Exelixis Inc. and Ipsen
and reflects solely the opinion of Exelixis and Ipsen. Nothing in this
statement shall be construed to imply any support or endorsement of
Exelixis or Ipsen, or any of its products, by the Regents of the
University of California, its officers, agents and employees.